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First described in the milkweed bug Oncopeltus fasciatus, planar cell polarity (PCP) is a developmental process essential for embryogenesis and development of polarized structures in Metazoans. This signaling pathway involves a set of evolutionarily conserved genes encoding transmembrane (Vangl, Frizzled, Celsr) and cytoplasmic (Prickle, Dishevelled) molecules. Vangl2 is of major importance in embryonic development as illustrated by its pivotal role during neural tube closure in human, mouse, Xenopus, and zebrafish embryos. Here, we report on the molecular and functional characterization of a Vangl2 isoform, Vangl2-Long, containing an N-terminal extension of about 50 aa, which arises from an alternative near-cognate AUA translation initiation site, lying upstream of the conventional start codon. While missing in Vangl1 paralogs and in all invertebrates, including Drosophila, this N-terminal extension is conserved in all vertebrate Vangl2 sequences. We show that Vangl2-Long belongs to a multimeric complex with Vangl1 and Vangl2. Using morpholino oligonucleotides to specifically knockdown Vangl2-Long in Xenopus, we found that this isoform is functional and required for embryo extension and neural tube closure. Furthermore, both Vangl2 and Vangl2-Long must be correctly expressed for the polarized distribution of the PCP molecules Pk2 and Dvl1 and for centriole rotational polarity in ciliated epidermal cells. Altogether, our study suggests that Vangl2-Long significantly contributes to the pool of Vangl2 molecules present at the plasma membrane to maintain PCP in vertebrate tissues., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Planar cell polarity (PCP) refers to the capacity of a tissue, typically, but not exclusively, an epithelium, to transmit directional information across the tissue plane such that its cellular constituents can differentiate, divide or move in a coordinated manner and along a common axis, generally orthogonal to the apical-basal axis. PCP relies on a core module of highly conserved proteins originally identified in Drosophila which can act intra- and extracellularly. In this review, we focus on the vertebrate ortholog of one of these core PCP components, namely the Vangl2 protein. After a brief historical perspective, we discuss novel cellular settings for which a cellular Vangl2 requirement has been recently documented, with a particular emphasis on adult tissues that rely on Vangl2 for the maintenance of their regenerative capacity or their physiological functions. Finally we compile the most recent data about Vangl2 interacting proteins., (Copyright © 2017 Elsevier Ltd. All rights reserved.)